Pharmacokinetics of Omeprazole and Midazolam When Co-administered With ACT-1014-6470

• Sponsor: Idorsia Pharmaceuticals Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05123820
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Actual Duration (Days): 11
• Patients Per Site Per Month: 55.3

Study Details

Study Description

Brief Summary

A study on whether ACT-1014-6470 has an effect on how the body takes up, distributes and gets rid of omeprazole and midazolam in healthy male subjects

Condition or Disease	Intervention/Treatment	Phase
Drug Drug Interaction; Healthy	Drug: Treatment period A; Drug: Treatment period B	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Two-period, fixed-sequence studyTwo-period, fixed-sequence study
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Single-center, Open-label, Two-period, Fixed-sequence Study to Investigate the Effect of a Single Oral Dose of ACT-1014-6470 on the Pharmacokinetics of Omeprazole, Midazolam, and Their Metabolites in Healthy Male Subjects
• Actual Study Start Date: Nov 13, 2021
• Actual Primary Completion Date: Nov 24, 2021
• Actual Study Completion Date: Nov 24, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: ACT-1014-6470, Midazolam and Omeprazole Treatment Period A (Day 1 to Day 2) The plan is that all participants will receive treatment A and then treatment B. A single oral dose of midazolam 2 mg and a single oral dose of omeprazole 20 mg on Day 1. Treatment Period B (Day 8 to Day 11) A single oral dose of 100 mg ACT-1014-6470, a single oral dose of 20 mg omeprazole, and a single oral dose of 2 mg midazolam on Day 8.

Drug: Treatment period A; Midazolam solution for oral administration. Omeprazole hard capsule for oral administration.; Other Names: Midazolam and Omeprazole ; Drug: Treatment period B; ACT-1014-6470 soft capsule for oral administration. Midazolam solution for oral administration. Omeprazole hard capsule for oral administration.; Other Names: ACT-1014-6470, Midazolam and Omeprazole

Outcome Measures

Primary Outcome Measures

1. Maximum plasma concentration (Cmax) of ACT-1014-6470, midazolam and omeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

2. Time to reach Cmax (tmax) of ACT-1014-6470, midazolam and omeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

3. The area under the plasma concentration-time curve (AUC) from zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of ACT-1014-6470, midazolam and omeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

4. Area under the plasma concentration-time curve [AUC(0-12)] of omeprazole. [Total duration: up to 9 days]

   The plasma pharmacokinetic parameters of omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profile.

5. Area under the plasma concentration-time curve [AUC(0-24)] of midazolam and omeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

6. Area under the plasma concentration-time curve [AUC(0-inf)] of ACT-1014-6470, midazolam and omeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

7. Apparent total body clearance (CL/F) of ACT-1014-6470, midazolam and omeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

8. The terminal half-life (t½) of ACT-1014-6470, midazolam and omeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

Secondary Outcome Measures

1. Maximum plasma concentration (Cmax) of 1-hydroxymidazolam and 5-hydroxyomeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

2. Time to reach Cmax (tmax) of 1-hydroxymidazolam and 5-hydroxyomeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

3. The area under the plasma concentration-time curve (AUC) from zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of 1-hydroxymidazolam and 5-hydroxyomeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

4. Area under the plasma concentration-time curve [AUC(0-12)] of 5-hydroxyomeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

5. Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam and 5-hydroxyomeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

6. Area under the plasma concentration-time curve [AUC(0-inf)] of 1-hydroxymidazolam and 5-hydroxyomeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

7. The terminal half-life (t½) of 1-hydroxymidazolam and 5-hydroxyomeprazole. [Total duration: up to 11 days]

   The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.

8. The metabolic ratio (MR) of 1-hydroxymidazolam to midazolam . [Total duration: up to 11 days]

9. The metabolic ratio (MR) of 5-hydroxyomeprazole to omeprazole. [Total duration: up to 11 days]

10. Number of participants with treatment-emergent adverse events as a measure of safety and tolerability. [Total duration: up to 11 days]

    An adverse event is an unfavorable and unintended sign (including an abnormal laboratory finding, an abnormal electrocardiogram). A treatment-emergent adverse event is any adverse event temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.

• Healthy male participant aged between 18 and 45 years (inclusive) at Screening.

• Body mass index of 18.5 to 28.0 kg/m2 (inclusive) at Screening.

• Systolic blood pressure 100-140 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute (inclusive), measured on either arm, after 5 min in the supine position at Screening and on Day -1.

Exclusion Criteria:

• Previous exposure to ACT-1014-6470.

• Known hypersensitivity to ACT-1014-6470, omeprazole, substituted benzimidazoles, midazolam, or treatments of the same pharmacological classes, or any of their excipients.

• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment (appendectomy and herniotomy allowed if performed more than 12 weeks prior to administration of [first] study treatment, cholecystectomy not allowed).

• Previous treatment with any prescribed medications (including vaccines [Vaccination regimen against COVID-19 completed less than 2 weeks prior to first study treatment administration or any vaccination against COVID-19 planned before end-of-study]) or over-the-counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 3 weeks prior to first study treatment administration.

• Legal incapacity or limited legal capacity at Screening.

• Participant with rare inherited issues of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CEPHA s.r.o.	Pilsen		Czechia	32300

Sponsors and Collaborators

• Idorsia Pharmaceuticals Ltd.

Investigators

• Study Director: Clinical Trials, Idorsia Pharmaceuticals Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Idorsia Pharmaceuticals Ltd.
• ClinicalTrials.gov Identifier: NCT05123820
• Other Study ID Numbers: ID-087-105; 2021-003615-26
• First Posted: Nov 17, 2021
• Last Update Posted: Jan 14, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Idorsia Pharmaceuticals Ltd.: ACT-1014-6470; Omeprazole; Midazolam
• Additional relevant MeSH terms: Midazolam; Omeprazole

Study Results

No Results Posted as of Jan 14, 2022